Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montréal, Canada.
Department of Pharmacy, Centre Hospitalier de l'Université de Montréal, Montréal, Canada.
Clin Transplant. 2022 Aug;36(8):e14709. doi: 10.1111/ctr.14709. Epub 2022 Jun 1.
Voriconazole is the first line treatment for invasive aspergillosis (IA) Current guidelines suggest performing regular voriconazole therapeutic drug monitoring (TDM) to optimize treatment efficacy. We aimed to determine if TDM was predictive of clinical outcome in LTRs.
Retrospective chart review was performed for all LTRs with probable or proven IA, treated with voriconazole monotherapy and who underwent TDM during therapy. Clinical outcome and toxicity were measured at 12 weeks. Classification and regression tree (CART) analysis was used to determine the most predictive voriconazole level thresholds for successful outcome.
One hundred and eighteen TDM samples from 30 LTRs with IA were analyzed. Three LTRs were excluded due to early treatment discontinuation. The median TDM level was 1.2 μg/ml (range 0.06-7.3). At 12 weeks, 62% (17/27) of patients had a successful outcome, while 37% (10/27) of patients failed therapy. CART analysis determined that the best predictor for successful outcome was a median TDM level >0.72 μg/ml. Seventy percent (14/20) of patients with median TDM above 0.72 μg/ml had a successful outcome, compared to 42.9% (3/7) of patients with a median TDM below 0.72 μg/ml (OR 3.11; 95% CI: 0.53-20.4; P = 0.21). CART analysis determined that a TDM level greater than 2.13 μg/ml was predictive of hepatotoxicity.
Our data suggests that a voriconazole TDM range between 0.72 μg/ml and 2.13 μg/ml may be associated with improved outcomes. Our study is in line with current recommendations on the use of voriconazole TDM in improving outcome and minimizing toxicity in LTR with IA.
伏立康唑是侵袭性曲霉病（IA）的一线治疗药物。目前的指南建议定期进行伏立康唑治疗药物监测（TDM），以优化治疗效果。我们旨在确定 TDM 是否可预测长期接受抗逆转录病毒治疗（LTR）患者的临床结局。
对所有接受伏立康唑单药治疗且治疗过程中进行 TDM 的疑似或确诊 IA 的 LTR 进行回顾性病历分析。在 12 周时评估临床结局和毒性。使用分类和回归树（CART）分析确定预测治疗成功的最具预测性伏立康唑水平阈值。
对 30 例 IA 患者的 118 个 TDM 样本进行了分析。由于早期停药，有 3 例 LTR 被排除。TDM 水平中位数为 1.2μg/ml（范围 0.06-7.3）。在 12 周时，62%（17/27）的患者治疗成功，而 37%（10/27）的患者治疗失败。CART 分析确定，预测治疗成功的最佳指标是 TDM 中位数>0.72μg/ml。TDM 中位数大于 0.72μg/ml 的 70%（14/20）患者治疗成功，而 TDM 中位数小于 0.72μg/ml 的患者 42.9%（3/7）治疗成功（OR 3.11；95%CI：0.53-20.4；P=0.21）。CART 分析确定，TDM 水平大于 2.13μg/ml 与肝毒性相关。
我们的数据表明，伏立康唑 TDM 范围在 0.72μg/ml 至 2.13μg/ml 之间可能与改善结局相关。我们的研究符合当前关于使用伏立康唑 TDM 改善 LTR 中 IA 的结局和降低毒性的建议。
